Practice question

Somatic gene therapy restricts genetic modification to differentiated somatic lineages such as hematopoietic stem cells, hepatocytes, myofibers, retinal pigment epithelium, or T lymphocytes, preserving integrity of primordial germ cells in gonadal ridges. Recombinant lentiviral vectors pseudotyped with VSV-G bind LDL receptor, entering CD34+ stem cells after cytokine stimulation with SCF, TPO, FLT3L that drives cell cycling required for reverse transcription and integration. Integrated provirus flanked by LTRs replicates synchronously with host chromosomes during mitosis, ensuring inheritance by progenitor progeny, while AAV episomes form circular concatemers persisting in post-mitotic nuclei. Because spermatogonia and oocytes lack vector exposure and meiosis transmits unmodified genome, correction remains limited to treated individual without transmission to offspring via Mendelian inheritance. This biological containment reduces ethical concerns, restricts insertional oncogenesis risk to one generation, permits localized dosing, and underlies acceptance for ADA deficiency and hemophilia. This mechanistic insight guides vector optimization, dosing strategies, and clinical safety monitoring essential for translational development and regulatory evaluation.